Acusphere uses polymer technology to extend life of ultrasound contrast

Potential $1 billion market awaits products

A newcomer to the market for ultrasound contrast agents hopesto extend the in vivo lifespan of contrast agents with a methodof using synthetic polymers to encase echogenic substances. Acusphereof Wellesley, MA, has received venture capital financing to commercializea product that may last longer in the bloodstream than other agentsin development.

The ultrasound contrast market could prove lucrative. A Hambrecht& Quist report placed the U.S. market for intravenous ultrasoundcontrast agents for myocardial perfusion at potentially $1 billion.Several developers have products in clinical trials or awaitingFood and Drug Administration approval. Most notable among themis Molecular Biosystems, which received an "approvable letter"from the agency in April for its Albunex agent (SCAN 5/4/94).

Acusphere is planning to tap into this market by developingtiny microcapsules made from synthetic polymers. The microcapsulesencase substances that can be used as ultrasound contrast agents,such as air, which is highly echogenic.

The use of polymers to make contrast agents is not new. Albunex,for example, is made from a natural polymer based on albumin,a protein. There are disadvantages to going natural, however,according to Acusphere president and CEO Sherri C. Oberg. Naturalpolymers are more expensive to manufacture, must be purified,and the properties of the polymers can vary from batch to batch,she said.

Contrast agents based on synthetic polymers would overcomethese obstacles, but most synthetic polymers are turned into microcapsulesusing either heat or organic solvents, which can destroy the substancesthat are being encapsulated.

Acusphere's synthetic polymer microcapsules are manufacturedwithout the use of heat or organic solvents. The technology wasinvented by Smadar Cohen and Robert S. Langer of the MassachusettsInstitute of Technology in Cambridge, MA, and Harry R. Allcockof Pennsylvania State University in University Park, PA. Langer,Allcock and Oberg formed Acusphere last year to commercializethe technology. The start-up received venture capital fundingin March.

One of the first applications for Acusphere's technology willbe ultrasound contrast agents. Acusphere's agents are based ontwo types of synthetic polymers: one called polyphosphazenes,and the other a substance the company has declined to specifyfor proprietary reasons. The FDA has approved the substance foruse in the human body in other applications, according to thecompany.

A major advantage of Acusphere's technology is that it permitsthe development of contrast agents that are very stable in thebody and thus have long in vivo persistence times. Preliminaryechogenicity studies on animals indicate that Acusphere's microcapsulescan provide enhancement for at least 20 minutes, according toOberg. Contrast agents under development at other companies havepersistence times of 10 minutes at most, she said.

"The principal problem with the other contrast agentsis stability -- they don't stay in the blood stream very longand they end up degrading," Oberg said. "As a result,you can't use them for myocardial perfusion, which is what everyonewould like to diagnose."

Acusphere's lead product, based on the as-yet undisclosed substance,would be an injectable agent. The company has not decided whatapplications the agent would target, but myocardial perfusionwould be a good bet. The product is in preclinical trials.

Acusphere received a patent on its core microencapsulationtechnology, bringing to four the number of patents it has beenissued. Research on the technology is continuing at the Centerfor Imaging and Pharmaceutical Research at Massachusetts GeneralHospital.

Acusphere's technology might be applicable to MRI contrastagents, by encapsulating paramagnetic particles instead of air,Oberg said. The technology could also be used for CT blood-poolagents, which are used to image blood perfusion in tissue.